Is the TSHR D727E polymorphism a genetic predisposition for multinodular goiter in the Turkish population?

Abstract

ABSTRACT. The D727E germline polymorphism in the thyroidstimulating hormone receptor gene (TSHR) may cause genetic susceptibility to the development of goiter. Therefore, in this study we investigated allele frequencies and genotype distributions of the TSHR D727E polymorphism, their association with clinical parameters, and the development of goiter in the Turkish population. We investigated the TSHR D727E polymorphism in 123 patients and 97 healthy subjects using the polymerase chain reaction-restriction fragment length polymorphism technique. Peripheral blood was used for DNA 2 H.I. Gözü et al. Genetics and Molecular Research 15 (3): gmr.15038504 extraction. Although no significant difference was found in TSHR D727E polymorphism frequencies between the patients with nodular goiters (26/123 patients, 21.1%) and the controls (12/97 patients, 12.4%) (P = 0.107), the frequency of the TSHR D727E polymorphism in the hyperthyroid+subclinical hyperthyroid patient groups (23%) was significantly higher than in the control subjects (12.4%) (P = 0.024). In this study, nodular goiter presented significantly earlier in GC genotype patients (mean age 35 years) than in CC genotype patients (mean age 42 years) in the hyperthyroid group (P = 0.009). More importantly, TSH levels in the GC variant controls were closely significant lower (1.26 ± 0.49) than in the CC variant controls (1.74 ± 0.84) (P = 0.053). The TSHR D727E polymorphism might be involved in the pathogenesis of toxic multinodular goiter (TMNG). Moreover, this polymorphism might be an indication of early-onset TMNG. However, development of MNG is multifactorial. Therefore, further case-control studies with larger populations are required to verify these observations.

The activity of proliferation and apoptosis of thyrocytes in the thyroid tissue of patients of nodular goiter with autoimmune thyroiditis considering the polymorphism of the BCL-2 (RS17759659), CTLA-4 (RS231775), APO-1/FAS (RS2234767) genes

“…The function of anti-apoptotic protein p53 is to remove the cells that are potentially oncogenic out of the pool. In almost 50% of cases of human cancers, the loss of protein p53 function is diagnosed [10][11][12][13][14][15][16][17][18].…”

Molecular-genetic mechanisms in development of degree of function and hyperplasia of thyroid gland of patients with nodular goiter with autoimmune thyroiditis and thyroid adenoma

“…Nodular goiter is considered as a non-autoimmune thyroid disease, and there have been findings to support this hypothesis (4)(5)(6). However, several immunological alterations have been found in these patients, such as HLA-DR antigen expression in thyrocytes, the presence of growth-stimulating immunoglobulins, and an increase in dendritic cells and lymphocytes, which suggest the possibility of autoimmune problems (1,(8)(9)(10). Although many of these findings may be an epiphenomenon of other primary defects in immunoregulation, the alteration of lymphocyte populations indicates a primary defect (6,7,10,(12)(13)(14)(15)(16)(17)(18).…”

“…Variations in several genes have been studied as possible risk factors for Hashimoto thyroiditis. Some of these genes are part of a family called the human leukocyte antigen (HLA) complex (8)(9)(10). The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders (such as viruses and bacteria).…”

“…AIT thought to result from a combination of genetic and environmental factors (1)(2)(3)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Some of these factors have been identified, but many remain unknown (19)(20)(21)(22)(23)(24).…”

Поліморфізм генів apo-1 / fas, ctla-4 та bcl-2 у пацієнтів, оперованих із приводу вузлової патології щитоподібної залози

“…В основі розвитку авто-імунних захворювань щитоподібної залози лежить взаємодія генетичних факторів і тригерів навко-лишнього середовища, що призводить до вислизан-ня від механізму власної імунологічної толерант-ності [1][2][3]. Непрямим підтвердженням існу вання генетичного компонента є висока поширеність сі-мейних випадків автоімунних захворювань щито-подібної залози (ЩЗ), яка може бути виявлена в кожному третьому випадку [19,20]. Різні дослід-ницькі групи протягом багатьох років не одноразово вказували, що особи з обтяженим сімейним анам-незом щодо захворювань ЩЗ мають більший ризик виникнення даної патології.…”